The control of erythroid differentiation of Friend Leukemia cells will be analyzed at a molecular and cellular level. Three interacting lines of investigation will be pursued: 1) Genetic analysis of differentiation by Friend cells. Genetic analysis will commence with the isolation and examination of cell lines that appear to have altered control of the differentiation process. We have obtained cell lines which do not respond to DMSO (an inducer of erythroid differentiation in wild type Friend cells) and cell lines which differentiate to a significant degree in the absence of DMSO. A further goal will be to obtain and characterize cell lines temperature-sensitive for inducibility or expression of the differentiated phenotype. 2) Biochemical analysis of globin mRNA synthesis and stability under controlled genetic and physiological conditions. This analysis will require the use of a synthetic DNA copy (cDNA) of purified alpha and beta globin chain mRNAs in hybridization experiments to quantitate the rate of transcription, nuclear processing and cytoplasmic degradation of globin mRNA sequences. 3) Application of cell separation techniques to purify homogeneous Friend cell populations with respect to extent of differentiation or commitment to differentiation. BIBLIOGRAPHIC REFERENCES: Forget, B., Hillman, D.H., Lazarus, H., Barell, E.F., Benz, E.J., Caskey, C.T., Huisman, T.H.J., Schroeder, W.A. and Housman, D.: Absence of Messenger RNA and Gene DNA for Beta Globin Chains in Hereditary Persistence of Fetal Hemoglobin. Cell 7: 323-329, 1976. Gusella, J. and Housman, D.: Induction of Erythroid Differentiation in vitro by Purines and Purine Analogues. Cell 8: 263-269, 1976.